tbuckley/cabot-search huggingface dataset:
Age Disparities in Prevalence of Anxiety and Depression Among US Adults During the COVID-19 Pandemic
Authors: Sarah Collier Villaume, Shanting Chen, Emma K. Adam
Journal: JAMA Network Open (2023)

High levels of anxiety and depression were documented shortly after the arrival of the COVID-19 pandemic and were more prevalent in younger adults than in older adults. Knowing whether these age disparities persisted throughout multiple years of the COVID-19 pandemic and identifying associated factors will help guide health policy.To investigate age disparities in anxiety and depression during the COVID-19 pandemic.This cross-sectional study consisted of a nationally representative online survey administered between April 2020 and August 2022 and included US adults who were not incarcerated. Data were analyzed between March and September 2022.The first 27 months of the COVID-19 pandemic included wide variation in infection rates, turbulence in US political and social life, and geopolitical instability. Primary exposures include individuals' age and economic precarity and pandemic-related events (eg, weekly state-level case counts and individual vaccination status).Symptoms of anxiety and depression were assessed via responses to 2-item screeners (Generalized Anxiety Disorder 2-item for anxiety and Patient Health Questionnaire-2 for depression). An individual's symptoms were identified as clinically elevated if scores exceeded validated thresholds.This study included 3 028 923 respondents (mean [SD] age, 48.9 [17.0] years; 1 567 603 [51.8%] female). In multiple regression analyses that include state fixed effects and survey-week fixed effects, likely anxiety and depressive disorders among 291 382 (40%) and 238 505 (33%) of adults aged 18 to 39 years, respectively, compared with 357 820 (31%) and 274 534 (24%) of adults aged 40 to 59 years and 225 295 (20%) and 183 695 (16%) adults aged 60 years and older. Levels declined throughout the pandemic period for those aged 40 years and older but remained elevated for younger adults. Analyses identified several associated factors of these age disparities. Younger adults' anxiety and depression increased more than older adults' after surges in COVID-19 case counts but decreased less following vaccination against the virus. Additionally, approximately one third of the age gap among individuals with depression and anxiety was attributed to economic precarity, to which younger adults are disproportionately exposed.In this cross-sectional study of anxiety and depression during the COVID-19 pandemic, economic precarity was associated with high anxiety and depression among younger adults in the US compared with older adults in the US. These findings suggest a need for greater mental health care and economic policies targeted toward younger adults.
Structural Racism and Lung Cancer Risk
Authors: Sidra N. Bonner, Richard Curley, Kyra Love, Tola Akande, Aamna Akhtar, Loretta Erhunmwunsee
Journal: JAMA Oncology (2023)

Structural racism is associated with persistent inequities in health and health outcomes in the US for racial and ethnic minority groups. This review summarizes how structural racism contributes to differential population-level exposure to lung cancer risk factors and thus disparate lung cancer risk across different racial and ethnic groups.
Contemporary Trends in Reviewing Test Results Through the Electronic Patient Portal Among Patients With Cancer
Authors: Sheena Bhalla, Tanushree Prasad, Donglu Xie, David E. Gerber
Journal: JAMA Oncology (2023)

This cohort study among patients with cancer examines changes in the time from posting of test results in the electronic health record to patient viewing in the patient portal before and after implementation of the 21st Century Cures Act.
A Learning Program for Treatment Recommendations by Molecular Tumor Boards and Artificial Intelligence
Authors: Kuniko Sunami, Yoichi Naito, Yusuke Saigusa, Toraji Amano, Daisuke Ennishi, Mitsuho Imai, Hidenori Kage, Masashi Kanai, Hirotsugu Kenmotsu, Keigo Komine, Takafumi Koyama, Takahiro Maeda, Sachi Morita, Daisuke Sakai, Makoto Hirata, Mamoru Ito, Toshiyuki Kozuki, Hiroyuki Sakashita, Hidehito Horinouchi, Yusuke Okuma, Atsuo Takashima, Toshio Kubo, Shuichi Hironaka, Yoshihiko Segawa, Yoshihiro Yakushijin, Hideaki Bando, Akitaka Makiyama, Tatsuya Suzuki, Ichiro Kinoshita, Shinji Kohsaka, Yuichiro Ohe, Chikashi Ishioka, Kouji Yamamoto, Katsuya Tsuchihara, Takayuki Yoshino
Journal: JAMA Oncology (2023)

Substantial heterogeneity exists in treatment recommendations across molecular tumor boards (MTBs), especially for biomarkers with low evidence levels; therefore, the learning program is essential.
<i>KRAS</i> Sequence Variation as Prognostic Marker in Patients With Young- vs Late-Onset Colorectal Cancer
Authors: Mayada A. Aljehani, Jeffrey Bien, Jerry S. H. Lee, George A. Fisher, Albert Y. Lin
Journal: JAMA Network Open (2023)

Importance The understanding of the association between KRAS sequence variation status and clinical outcomes in colorectal cancer (CRC) has evolved over time. Objective To characterize the association of age at onset, tumor sidedness, and KRAS sequence variation with survival among patients diagnosed with CRC. Design, Setting, and Participants This cross-sectional study used data extracted from the Surveillance, Epidemiology, and End Results database. Patients diagnosed with adenocarcinoma of the colon or rectum from 2010 through 2015 were included and were classified as having young-onset (YO) cancer if diagnosed between ages 20 to 49 years and late-onset (LO) cancer if diagnosed at age 50 years or older. Data were analyzed from April 2021 through August 2023. Main Outcomes and Measures CRC cause-specific survival (CSS) was summarized using Fine and Gray cumulative incidence and Kaplan-Meier curves. Estimation of subdistribution hazard ratios (sHRs) for the association of KRAS status, age at onset, and tumor location with CRC CSS was conducted using the Fine and Gray competing risk model. Cox proportional hazards regression was used to estimate and compare HRs. Results Among 21 661 patients with KRAS sequence variation status (mean [SD] age at diagnosis, 62.50 [13.78] years; 9784 females [45.2%]), 3842 patients had YO CRC, including 1546 patients with KRAS variants, and 17 819 patients had LO CRC, including 7311 patients with KRAS variants. There was a significant difference in median CSS time between patients with variant vs wild-type KRAS (YO: 3.0 years [95% CI, 2.8-3.3 years] vs 3.5 years [95% CI, 3.3-3.9 years]; P = .02; LO: 2.5 years [95% CI, 2.4-2.7 years] vs 3.4 years [95% CI, 3.3-3.6 years]; P &amp;amp;lt; .001). Tumors with variant compared with wild-type KRAS were associated with higher risk of CRC-related death (YO: sHR, 1.09 [95% CI, 1.01-1.18]; P = .03; LO: sHR, 1.06 [95% CI, 1.02-1.09]; P = .002). Among patients with YO cancer, mortality hazards increased by location, from right (sHR, 1.02 [95% CI, 0.88-1.17) to left (sHR, 1.15 [95% CI, 1.02-1.29) and rectum (sHR, 1.16 [95% CI, 0.99-1.36), but no trend by tumor location was seen for LO cancer. Conclusions and Relevance In this study of patients diagnosed with CRC, KRAS sequence variation was associated with increased mortality among patients with YO and LO tumors. In YO cancer, variant KRAS– associated mortality risk was higher in distal tumors than proximal tumors.
Clinical and Immunologic Features of Germline Pathogenic Variant–Positive Patients with Melanoma
Authors: Alan Shen, Michelle Arbesman, Roshan Lodha, Patricia Rayman, Brandon Bungo, Ying Ni, Timothy Chan, Brian Gastman, Jennifer Ko, C. Marcela Diaz-Montero, Joshua Arbesman, Pauline Funchain
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Malignant melanoma represents the most lethal skin cancer with germline predispositions thought to comprise 10% to 15% of all melanoma cases. No studies to date examine the immunologic features that may differentiate survival differences between germline pathogenic variant (gPV)–positive patients with melanoma from gPV-negative patients with melanoma. Experimental Design: Adult patients with melanoma and clinical characteristics suggesting hereditary predisposition to cancer were prospectively recruited to undergo germline testing and flow cytometric analysis of peripheral immune suppressor cells. Results: In this cohort, gPV-positive patients (n = 72) had a significantly improved melanoma-specific survival (MSS) compared with gPV-negative patients (n = 411; HRadj, 0.32; 95% CI, 0.13–0.82; P = 0.01). These survival improvements among gPV-positive patients were most apparent among cutaneous melanoma subtypes (HRadj, 0.12; 95% CI, 0.016–0.86; P = 0.03) and numerically improved in later-stage (IIB–IV) patients (HRadj, 0.34; 95% CI, 0.10–1.11; P = 0.06). Further, gPV-positive patients had a significantly lower level of total circulating PMN-MDSC compared with gPV-negative patients (P = 0.01), which was most apparent in those diagnosed with later stages (IIB–IV) of melanoma (P = 0.009). Finally, a significant upregulation of inflammatory transcriptome signatures in later-stage gPV-positive patients (n = 21) was observed in comparison with gPV-negative patients (n = 173) in the cutaneous melanoma cohort (SKCM) of The Cancer Genome Atlas (TCGA). Conclusions: gPV-positive patients with melanoma exhibit improved MSS in addition to reduced peripheral PMN-MDSC and an enhanced inflammatory microenvironment.
Pancreatic Replacement Therapy for Maladaptive Behaviors in Preschool Children With Autism Spectrum Disorder
Authors: Deborah A. Pearson, Robert L. Hendren, Matthew F. Heil, William R. McIntyre, Shane R. Raines
Journal: JAMA Network Open (2023)

There is an urgent unmet need for a treatment addressing the core symptoms and associated maladaptive symptoms of autism spectrum disorder (ASD), especially in preschool populations.To evaluate whether treatment of children with ASD aged 3 to 6 years treated with high-protease pancreatic therapy produces long- and short-term improvements in autism-associated maladaptive behaviors.This cohort study at 32 sites across the US used a double-blind parallel group, delayed-start design comprising a 2-week blinded placebo run-in, and a double-blind, randomized, placebo-controlled segment (12 weeks). Children were recruited into the study in 2015, with data collection continuing until 2021. The analyses were completed from June 2021 to February 2022.All participants were randomly assigned to receive either 900 mg high-protease pancreatic replacement therapy or placebo with food 3 times a day for 12 weeks, followed by all receiving 900 mg high-protease pancreatic replacement therapy for 24 weeks.The primary outcome was the irritability/agitation subscale of the Aberrant Behavior Checklist (ABC-I). All potential participants were screened using the Social Communication Questionnaire (SCQ) with diagnosis confirmed by the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) for ASD and the Autism Diagnostic Inventory-Revised (ADI-R). Outcomes were measured at the conclusion of the 12-week double-blind segment and at the conclusion of the 24-week open-label segment (total 36 weeks).A total of 190 participants (150 male [79%]), aged 3 to 6 (mean [SD] age, 4.5 [0.8]) years were randomized. Mixed model for repeated measures analysis performed on ABC-I demonstrated statistically significant differences of -2.49 (95% CI, -4.66 to -0.32; Cohen d = 0.364; P = .03) at the 12-week timepoint and -3.07 (95% CI, -5.81 to -0.33; Cohen d = 0.516; P = .03) at 36-week timepoint. No convergence was noted. Our high-protease pancreatic replacement (CM-AT) was well tolerated with no emergent safety concerns or related serious adverse events noted.This cohort study of preschool children sustained cumulative reduction in the maladaptive behavior of irritability in autism. This delayed-start analysis, used to demonstrate disease and condition modification, may prove to be an important tool to evaluate treatments for ASD.ClinicalTrials.gov Identifier: NCT02410902 and NCT02649959.
Conscientious Objection to Aggressive Interventions for Patients in a Vegetative State
Authors: Jason Adam Wasserman, Abram L. Brummett, Mark Christopher Navin, Daniel Londyn Menkes
Journal: The American Journal of Bioethics (2023)

Some physicians refuse to perform life-sustaining interventions, such as tracheostomy, on patients who are very likely to remain permanently unconscious. To explain their refusal, these clinicians often invoke the language of "futility", but this can be inaccurate and can mask problematic forms of clinical power. This paper explores whether such refusals should instead be framed as conscientious objections. We contend that the refusal to provide interventions for patients very likely to remain permanently unconscious meets widely recognized ethical standards for the exercise of conscience. We conclude that conscientious objection to tracheostomy and other life-sustaining interventions on such patients can be ethical because it does not necessarily constitute a form of invidious discrimination. Furthermore, when a physician frames their refusal as conscientious objection, it makes transparent the value-laden nature of their objection and can better facilitate patient access to the requested treatment.
Spatiotemporally sequential delivery of biomimetic liposomes potentiates glioma chemotherapy
Authors: Muye Zhou, Yanping Wu, Mengjuan Sun, Yun Qin, Jianing Zhao, Zijie Qiu, Chunjiayu Li, Yue Zhang, Yerong Xiong, Yan Shen, Zhirui Zou, Jiasheng Tu, Weiyang Shen, Chunmeng Sun
Journal: Journal of Controlled Release (2023)
Fecal microbiota transplanted from old mice promotes more colonic inflammation, proliferation, and tumor formation in azoxymethane-treated A/J mice than microbiota originating from young mice
Authors: Nicholas A. Crossland, Samuel Beck, Wei Yu Tan, Ming Lo, Joel B. Mason, Chao Zhang, Weimin Guo, Jimmy W. Crott
Journal: Gut Microbes (2023)

Aging is a strong risk factor for colorectal cancer (CRC). It is well established that gut microbial dysbiosis can play a role in the etiology of CRC. Although the composition of the gut microbial community changes with age and is reported to become more pro-inflammatory, it is unclear whether such changes are also pro-tumorigenic for the colon. To address this gap, we conducted fecal microbiota transplants (FMT) from young (DY, ~6 wk) and old (DO, ~72 wk) donor mice into young (8 wk) recipient mice that were pre-treated with antibiotics. After initiating tumorigenesis with azoxymethane, recipients were maintained for 19 wk during which time they received monthly FMT boosters. Compared to recipients of young donors (RY), recipients of old donors (RO) had an approximately 3-fold higher prevalence of histologically confirmed colon tumors (15.8 vs 50%, Chi2 P = .03), approximately 2-fold higher proliferating colonocytes as well as significantly elevated colonic IL-6, IL-1β and Tnf-α. Transcriptomics analysis of the colonic mucosa revealed a striking upregulation of mitochondria-related genes in the RO mice, a finding corroborated by increased mitochondrial abundance. Amongst the differences in fecal microbiome observed between DY and DO mice, the genera Ruminoclostridium, Lachnoclostridium and Marvinbryantia were more abundant in DY mice while the genera Bacteroides and Akkermansia were more abundant in DO mice. Amongst recipients, Ruminoclostridium and Lachnoclostridium were higher in RY mice while Bacteroides was higher in RO mice. Differences in fecal microbiota were observed between young and old mice, some of which persisted upon transplant into recipient mice. Recipients of old donors displayed significantly higher colonic proliferation, inflammation and tumor abundance compared to recipients of young donors. These findings support an etiological role for altered gut microbial communities in the increased risk for CRC with increasing age and establishes that such risk can be transmitted between individuals.
Clinical Benefit of Avapritinib in <i>KIT-</i>Mutant Gastrointestinal Stromal Tumors: A <i>Post Hoc</i> Analysis of the Phase I NAVIGATOR and Phase I/II CS3007–001 Studies
Authors: Michael C. Heinrich, Xinhua Zhang, Robin L. Jones, Suzanne George, César Serrano, Yanhong Deng, Sebastian Bauer, Shirong Cai, Xin Wu, Yongjian Zhou, Kaixiong Tao, Zhichao Zheng, Jun Zhang, Yuehong Cui, Hui Cao, Meining Wang, Jin Hu, Jason Yang, Jian Li, Lin Shen
Journal: Clinical Cancer Research (2023)

Abstract Purpose: The efficacy of the selective KIT/PDGFRA inhibitor avapritinib (300 mg once daily) was explored in patients with non–PDGFRA-mutant gastrointestinal stromal tumors (GISTs) from the phase I NAVIGATOR and phase I/II CS3007–001 trials. Patients and Methods: Adults with unresectable/metastatic, KIT-only-mutant GISTs and progression following ≥1 tyrosine kinase inhibitors (TKIs) were included in this post hoc analysis. Baseline mutational status was identified in tumor and plasma. Primary endpoints were objective response rate (ORR) and progression-free survival (PFS) by blinded independent radiology review per modified RECIST v1.1 in patients harboring KIT activation-loop mutations (KIT exons 17 or 18) without ATP binding-pocket mutations (KIT exons 13 or 14; ALposABPneg), and other KIT mutations (OTHERS). Results: Sixty KIT ALposABPneg and 100 KIT OTHERS predominantly heavily pretreated patients (61.3% with ≥3 prior TKIs) were included. ORR was significantly higher in KIT ALposABPneg than KIT OTHERS patients (unadjusted: 26.7% vs. 12.0%; P = 0.0852; adjusted: 31.4% vs. 12.1%; P = 0.0047). Median PFS (mPFS) was significantly longer in KIT ALposABPneg patients compared with KIT OTHERS patients (unadjusted: 9.1 vs. 3.5 months; P = 0.0002; adjusted: 9.1 vs. 3.4 months; P &amp;lt; 0.0001), and longer in second- versus later-line settings (19.3 vs. 5.6–10.6 months). Benefit with avapritinib was observed in patients with KIT exon 9 mutations in the ≥4 line settings (mPFS: 5.6 and 3.7 months for 4 line and &amp;gt;4 line, respectively). Conclusions: Avapritinib showed greater antitumor activity in patients with GISTs harboring KIT ALposABPneg mutations versus KIT OTHERS, and may be considered in the former subpopulation. Patients with KIT exon 9 mutations may also benefit in ≥4 line settings.
Longitudinal asthma phenotypes by multi‐trajectory analysis
Authors: Duong Duc Pham, Chaelin Hong, Ji‐Hyang Lee, Hyouk‐Soo Kwon, Woo‐Jung Song, You Sook Cho, Ji Seon Oh, Tae‐Bum Kim
Journal: Allergy (2023)

The data that support the findings of this study are available from the corresponding author upon reasonable request. Data S1. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Transitional Care Interventions From Hospital to Community to Reduce Health Care Use and Improve Patient Outcomes
Authors: Natasha Tyler, Alexander Hodkinson, Claire Planner, Ioannis Angelakis, Christopher Keyworth, Alex Hall, Paul Pascall Jones, Oliver George Wright, Richard Keers, Tom Blakeman, Maria Panagioti
Journal: JAMA Network Open (2023)

Importance Discharge from the hospital to the community has been associated with serious patient risks and excess service costs. Objective To evaluate the comparative effectiveness associated with transitional care interventions with different complexity levels at improving health care utilization and patient outcomes in the transition from the hospital to the community. Data Sources CENTRAL, Embase, MEDLINE, and PsycINFO were searched from inception until August 2022. Study Selection Randomized clinical trials evaluating transitional care interventions from hospitals to the community were identified. Data Extraction and Synthesis At least 2 reviewers were involved in all data screening and extraction. Random-effects network meta-analyses and meta-regressions were applied. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. Main Outcomes and Measures The primary outcomes were readmission at 30, 90, and 180 days after discharge. Secondary outcomes included emergency department visits, mortality, quality of life, patient satisfaction, medication adherence, length of stay, primary care and outpatient visits, and intervention uptake. Results Overall, 126 trials with 97 408 participants were included, 86 (68%) of which were of low risk of bias. Low-complexity interventions were associated with the most efficacy for reducing hospital readmissions at 30 days (odds ratio [OR], 0.78; 95% CI, 0.66 to 0.92) and 180 days (OR, 0.45; 95% CI, 0.30 to 0.66) and emergency department visits (OR, 0.68; 95% CI, 0.48 to 0.96). Medium-complexity interventions were associated with the most efficacy at reducing hospital readmissions at 90 days (OR, 0.64; 95% CI, 0.45 to 0.92), reducing adverse events (OR, 0.42; 95% CI, 0.24 to 0.75), and improving medication adherence (standardized mean difference [SMD], 0.49; 95% CI, 0.30 to 0.67) but were associated with less efficacy than low-complexity interventions for reducing readmissions at 30 and 180 days. High-complexity interventions were most effective for reducing length of hospital stay (SMD, −0.20; 95% CI, −0.38 to −0.03) and increasing patient satisfaction (SMD, 0.52; 95% CI, 0.22 to 0.82) but were least effective for reducing readmissions at all time periods. None of the interventions were associated with improved uptake, quality of life (general, mental, or physical), or primary care and outpatient visits. Conclusions and Relevance These findings suggest that low- and medium-complexity transitional care interventions were associated with reducing health care utilization for patients transitioning from hospitals to the community. Comprehensive and consistent outcome measures are needed to capture the patient benefits of transitional care interventions.